Evaluation of optimal timing and therapeutic efficacy of radium-223 therapy for metastatic castration-resistant prostate cancer: a multicenter collaborative study

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BACKGROUND: Despite its demonstrated efficacy in prolonging overall survival (OS) and delaying skeletal-related events in the ALSYMPCA trial, the optimal timing of radium-223 initiation remains unclear. This study investigated factors influencing radium-223 treatment outcomes, including completion rates and survival. METHODS: This retrospective, multi-institutional study included 164 patients with metastatic castration-resistant prostate cancer (CRPC) who received radium-223 therapy. The primary endpoint was OS following radium-223 initiation. Secondary endpoints included factors associated with incomplete radium-223 treatment (< six cycles) and poor OS. Multivariate Cox regression and multivariate logistic regression analyses were conducted to identify prognostic factors. RESULTS: The median OS times after CRPC diagnosis and radium-223 initiation were 39 and 12.5 months, respectively. Kaplan-Meier analysis showed that the OS of patients who completed six cycles of radium-223 treatment was longer than that of those who did not (18 vs. 5 months; P < .001). Multivariate Cox analysis identified Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥ 1 (hazard ratio [HR] = 1.74, P = .046), PSA > 17 ng/ml (HR = 2.93, P < .001), and radium-223 incompletion (HR = 3.23, P < .001) as independent predictors of poor OS. The radium-223 completion rate was 68.3%, and incompletion was significantly associated with prior docetaxel use (odds ratio [OR] = 5.97, P = .001), bone pain (OR = 2.64, P = .024), and PSA > 17 ng/ml at the start of radium-223 treatment (OR = 3.12, P = .013). CONCLUSIONS: Completion of all six cycles of radium-223 treatment were associated with favorable survival outcomes in metastatic CRPC patients. Prior docetaxel use, bone pain, and elevated PSA levels were significant risk factors for radium-223 incompletion. These findings suggest the importance of initiating radium-223 earlier in the treatment course for patients with favorable clinical profiles to maximize the therapeutic benefits.